Peter I. Mackenzie, John O. Miners, Ross A. McKinnon
Polymorphisms in UDP Glucuronosyltransferase Genes: Functional Consequences and Clinical Relevance
As glucuronidation is a major process for the metabolism
and removal of lipophilic chemicals, polymorphic
variations in genes encoding the enzymes involved in
this process, the UDP glucuronosyltransferases (UGT),
may have a significant impact on our capacity to
detoxify and eliminate drugs and toxins. Although 24
human UGT genes have been identified to date, only
polymorphisms in five UGTs, viz. UGT1A1, UGT1A6,
UGT2B4, UGT2B7 and UGT2B15 have been described.
Polymorphisms in UGT1A1, the major bilirubin-glucuronidating
form, often result in a decreased capacity
to glucuronidate bilirubin, such as observed in Gilbert
Syndrome and some forms of perinatal jaundice. The
frequencies of individual UGT1A1 polymorphisms
show extensive variability across ethnic groups. Two
variants of UGT1A6 and UGT2B4 and one variant of
UGT2B7 and UGT2B15 have been identified. However,
the clinical significance of these variants is unclear.
More UGT polymorphisms will undoubtedly be discovered
when the human genome is sequenced. However,
unless the UGT in question is responsible for the
exclusive metabolism of a particular drug or chemical
(e.g. UGT1A1 and bilirubin) or is the predominant or
only UGT present in the cell, it is unlikely that these
polymorphisms will be of major clinical significance.
Clinical Chemical Laboratory Medicine, Walter de Gruyter
Print ISSN: 1434-6621
Volume: 38, 09/2000
Pages: 889 - 892
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